The effects of morphine treatment on the turnover of rat brain proteins will be studied in an effort to understand mechanisms of tolerance and dependence to narcotic analgesic drugs. Alterations in protein turnover specifically correlated with the tolerant-dependent state will be sought particularly in those subcortical regions and subcellular fractions of brain which have most strongly implicated in the pharmacological effects of morphine. Specifically the turnover rates (both synthesis and degradation) of the proteins in mitochondria, microsomes, axonal and neuronal cell membranes and various synaptosomal subfractions including the soluble proteins, mitochondria, synaptic vesicles and synaptic membranes isolated from the cortex, midbrain and striatum will be compared in morphine tolerant and dependent rats and in placebo treated controls. Synthesis rates will be determined by measurement of free and protein bound amino acid after continuous intravenous infusion of tyrosine and degradation rates by following the decay in specific radioactivity of acidic amino acids labeled by a single intraperitoneal injection of (14C)NaHCO3. A double isotope procedure will also be employed to determine relative degradation rates of these proteins.